Background. Current treatment of inflammatory bowel diseases (IBD) is far from ideal and many IBD patients (Pts) dissatisfied with conventional medications have turned to CAM hoping to find more efficacy and less toxicity. Mounting evidence indicates that stressful experiences (stressors) trigger flare-up and/or worsen IBD's course, and our pilot data and review of the literature indicate that IBD Pts have high levels of stress (more frequent and more severe responses to stressors). High stress can activate the brain gut axis (BGA), cause intestinal mast cells to release proinflammatory mediators, and create a proinflammatory / prooxidant milieu in the gut, which increases the risk for flare-up. We surmised that CAM-based stress reduction techniques might prevent these effects. This is innovative as conventional therapies focus on attenuating mucosal immuno- inflammatory responses while our approach focuses on preventing them. The mindfulness based stress reduction (MBSR) program is a widely-used CAM intervention that reduces stress responses attenuates inflammation, and promotes normal immune functioning in a variety of health conditions. But MBSR has not been tested in IBD, and mechanisms underlying its various effects are largely unknown. Hypotheses: MBSR will reduce stress responses, normalize the gut milieu, and decrease flare-up frequency & severity in IBD Pts. Aims. To determine whether stress-reduction associated with 1 y of MBSR practice by Pts with moderately severe ulcerative colitis (UC), but who are in remission attenuates or prevents inflammation, oxidative tissue injury and flare-up. Methods: We will enroll 100 Pts in a Phase I/IIa randomized, double-blind, placebo- controlled trial. Pts will be assigned to (a) MBSR training (group sessions, 1.5 h each, 8 wks; n=50 ;) or (b) a time & attention control group (n=50) with similar sessions but only non-IBD focused educational information through structured lectures. Both groups will be followed for 1 y or until flare up. Predictions: (1) primary outcome MBSR will decrease gut inflammation (stool Calprotectin); (2) secondary outcomes MBSR will decrease oxidative tissue injury (mucosal protein oxidation), decrease stress responses (24 h urinary cortisol, ACTH, psych. questionnaires), prevent flare-up (clinical, endoscopic & histological indices), and be well- accepted and tolerated (structured questionnaires, rate of refusal to participate, drop-out rate). Significance: Validating our hypotheses will (1) establish proof of concept for use of MBSR in preventing flare up in IBD, (2) inform a future clinical trial (we envision an R01) regarding effect size, feasibility (acceptance and tolerance of MBSR) and appropriate control groups, (3) clarify the role of stress in IBD and mechanisms for MBSR effects. [unreadable] [unreadable] [unreadable]